Efficacy and Safety of BIA 9-1067 in Idiopathic Parkinson's Disease Patients. (BIPARKII)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bial - Portela C S.A.
ClinicalTrials.gov Identifier:
NCT01227655
First received: October 22, 2010
Last updated: January 12, 2015
Last verified: January 2015
  Purpose

Parkinson's disease (PD) is a neurodegenerative disorder of unknown aetiology with an estimated incidence of 4.5-16/100,000 persons/year.

BIA 9-1067 is currently being developed by BIAL (Portela & Cª,S.A.) to be used in addition to L-DOPA (Levodopa) /carbidopa or L-DOPA (Levodopa) / preparations in PD patients. Promising results have been obtained for BIA 9-1067 in previous studies.


Condition Intervention Phase
Parkinson's Disease
Drug: BIA 9-1067
Drug: Placebo
Drug: Levodopa
Drug: Carbidopa
Drug: Benserazide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of BIA 9-1067 in Idiopathic Parkinson's Disease Patients With "Wearing-off" Phenomenon Treated With Levodopa Plus a Dopa Decarboxylase Inhibitor (DDCI): a Double-blind, Randomised, Placebo-controlled, Parallel-group, Multicentre Clinical Study.

Resource links provided by NLM:


Further study details as provided by Bial - Portela C S.A.:

Primary Outcome Measures:
  • Efficacy of 2 BIA 9-1067 (25 mg, and 50 mg) Compared With Placebo, When Administered With the Existing Treatment of L-DOPA Plus a DDCI (DOPA Decarboxylase Inhibitor) [ Time Frame: 14-15 weeks ] [ Designated as safety issue: No ]
    Efficacy of 2 BIA 9-1067 (25 mg, and 50 mg) compared with placebo, when administered with the existing treatment of L-DOPA plus a DDCI (DOPA decarboxylase inhibitor), in patients with PD and end-of-dose motor fluctuations. The primary efficacy variable will be the change from baseline in absolute OFF-time at the end of the DB period.


Secondary Outcome Measures:
  • UPDRS (Unified Parkinson's Disease Rating Scale) Sections I (ON), II (ON and OFF), and III (ON) [ Time Frame: 14-15 weeks ] [ Designated as safety issue: No ]

    Total UPDRS SCORE (I, II (ON), and III) Change from Baseline to Endpoint

    • UPDRS I evaluation of mentation, behavior, and mood
    • UPDRS II self-evaluation of the activities of daily life (ADLs) including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food
    • UPDRS III clinician-scored monitored motor evaluation The UPDRS I, II and III scores and subscores are calculated as the sum of all individual items. If one or two items in a scale are missing, they will be imputed with the mean of the non-missing items of that scale.

    Subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe

    The final cumulative score will range from 0 (no disability) to 199 (total disability).


  • Parkinson's Disease Sleep Scale (PDSS) [ Time Frame: 14-15 weeks ] [ Designated as safety issue: No ]

    The Parkinson's disease Sleep Scale (PDSS) is a specific scale for the assessment of sleep disturbances in subjects with PD. The PDSS score is calculated as the sum of all single items. If one or two items are missing, they will be imputed with the mean of the non-missing items. If three or more items are missing, no imputation will be done and the score will be set to missing.

    Subscale has 0-10 ratings, where 0 = severe and 10 = normal

    The PDSS total score is a sum score of all 15 questions and ranges from 0 to 150, with lower scores meaning more disability.


  • Non-motor Symptoms Scale (NMSS) [ Time Frame: 14-15 weeks ] [ Designated as safety issue: No ]

    The Non-motor Symptoms Scale (NMSS) consists of 30 questions, covering 9 dimensions, whereby each item is scored for severity and frequency: Severity None 0 Mild (symptoms present but causes little distress) 1 Moderate (some distress or disturbance to subject) 2 Severe (major source of distress or disturbance to subject) 3

    Frequency Rarely (<1/wk) 1 Often (1/wk) 2 Frequent (several times per week) 3 Very Frequent (daily or all the time) 4

    The product of frequency and severity is calculated for each item and each dimension score is defined as the sum of the frequency*severity of the respective items. If frequency or severity of a single item is missing, the domain score will not be calculated. The NMSS total score is defined as the sum of all domain scores.

    The NMSS total score is calculated by adding all domain scores (0-360), and lower scores mean less disability.



Enrollment: 427
Study Start Date: March 2011
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIA 9-1067 25 mg once daily (QD).
BIA 9-1067, OPC, Opicapone 25 mg once daily (QD).
Drug: BIA 9-1067
Capsules will be used.
Other Name: Opicapone
Drug: Levodopa
Other Name: L-Dopa
Drug: Carbidopa
DOPA decarboxylase inhibitor (DDCI)
Drug: Benserazide
DOPA decarboxylase inhibitor
Experimental: BIA 9-1067 50 mg once daily (QD).
BIA 9-1067, OPC, Opicapone 50 mg once daily (QD).
Drug: BIA 9-1067
Capsules will be used.
Other Name: Opicapone
Drug: Levodopa
Other Name: L-Dopa
Drug: Carbidopa
DOPA decarboxylase inhibitor (DDCI)
Drug: Benserazide
DOPA decarboxylase inhibitor
Placebo Comparator: Placebo
PLC, Placebo
Drug: Placebo
comparator
Other Name: placebo; PLC
Drug: Levodopa
Other Name: L-Dopa
Drug: Carbidopa
DOPA decarboxylase inhibitor (DDCI)
Drug: Benserazide
DOPA decarboxylase inhibitor

Detailed Description:

This study aims to demonstrate the efficacy and safety of BIA 9-1067 used in addition to L-DOPA/DDCI to control the "wearing-off" phenomenon in patients with PD.

DDCI (DOPA decarboxylase inhibitors): benserazide and carbidopa

  Eligibility

Ages Eligible for Study:   30 Years to 83 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Able to comprehend and willing to sign an informed consent form.
  2. Male and female subjects between 30 and 83 years old, inclusive.
  3. Diagnosed with idiopathic PD according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria (UKPDSBBCDC) for at least 3 years.
  4. Disease severity Stages I-III (modified Hoehn &Yahr staging) at ON.
  5. Treated with L-DOPA/DDCI for at least 1 year with clear clinical improvement.
  6. Treated with 3 to 8 daily doses of L-DOPA/DDCI, which can include a slow-release formulation.
  7. On a stable regimen of L-DOPA/DDCI and other anti-PD drugs for at least 4 weeks before screening.
  8. Signs of "wearing-off" phenomenon (end-of-dose deterioration) for a minimum of 4 weeks before screening with average total daily OFF time while awake of at least 1.5 hours, excluding the early morning pre-first dose OFF, despite optimal anti-PD therapy (based on the investigator's judgment.

Exclusion Criteria:

  1. Non-idiopathic PD (atypical parkinsonism, secondary [acquired or symptomatic] parkinsonism, Parkinson-plus syndrome).
  2. Dyskinesia disability score >3 in the Unified Parkinson's Disease Rating Scale UPDRS) Sub-section IV A, item 33.
  3. Severe and/or unpredictable OFF periods.
  4. Treatment with prohibited medication: entacapone, tolcapone, neuroleptics, venlafaxine, MAO inhibitors (except selegiline up to 10 mg/day in oral formulation or 1.25 mg/day in buccal absorption formulation or rasagiline up to 1mg/day), or antiemetics with antidopaminergic action (except domperidone) within the month before screening.
  5. Treatment with apomorphine within the month before screening or likely to be needed at any time during the study.
  6. Dosage change of concomitant anti-PD medication within 4 weeks of screening.
  7. Previous or planned (during the entire study duration, including the OL period)deep brain stimulation.
  8. Previous stereotactic surgery (e.g. pallidotomy, thalamotomy) for PD or with planned stereotactic surgery during the study period.
  9. Any investigational medicinal product (IMP) within the 3 months (or within 5 half-lives, whichever is longer) before screening.
  10. Any medical condition that might place the subject at increased risk or interfere with assessments.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01227655

Locations
Portugal
Bial - Portela & Cª, S.A.
S. Mamede do Coronado, Portugal, 4745-457
Sponsors and Collaborators
Bial - Portela C S.A.
  More Information

No publications provided

Responsible Party: Bial - Portela C S.A.
ClinicalTrials.gov Identifier: NCT01227655     History of Changes
Other Study ID Numbers: BIA-91067-302, 2010-022366-27, BIA-91067-302
Study First Received: October 22, 2010
Results First Received: November 26, 2014
Last Updated: January 12, 2015
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Belgium: Federal Agency for Medicinal Products and Health Products
Estonia: The State Agency of Medicine
Czech Republic: State Institute for Drug Control
Israel: Ministry of Health
Australia: National Health and Medical Research Council
India: Central Drugs Standard Control Organization
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Chile: Instituto de Salud Pública de Chile
South Africa: Medicines Control Council
South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Bial - Portela C S.A.:
Parkinson
PD
Wearing-off
Levodopa/DDCI

Additional relevant MeSH terms:
Parkinson Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Parkinsonian Disorders
Levodopa
Anti-Dyskinesia Agents
Antiparkinson Agents
Central Nervous System Agents
Dopamine Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on May 29, 2015